第一部分  中国城镇地区系统性红斑狼疮流行病学调查

背景：系统性红斑狼疮（systemic lupus erythematosus, SLE）作为一种常见的慢性风湿免疫性疾病，已成为全球公共卫生关注的问题。然而，对于发展中国家SLE流行情况的认识仍相对有限。

方法：本研究利用2013至2017年期间23个省份的城镇职工医疗保险和城镇居民基本医疗保险数据进行全国性人群研究。根据疾病分类代码及诊断词筛选SLE病例，采用两阶段泊松回归模型估算了SLE的全国、年龄、性别及地区分层的粗患病率、发病率以及标化患病率、发病率。同时估算2017年中国SLE相关就医费用。

结果：共纳入SLE患者132,258例, 平均年龄43.03 (15.29) 岁，其中女性占81.33%。2017年中国城镇地区总人群、女性和男性中的SLE标准化患病率分别为 47.61、94.16和17.86每10万人。5年期间SLE的患病率年均增幅为21.50%。2017年中国城镇地区SLE标准化发病率为14.09 (95%CI：11.95-16.41) /10万人年，其中女性26.41/10万人, 男性5.92/10万人。2017年我国不同年龄段SLE患病率以及发病率均呈单峰分布, 女性高峰年龄段为30-39岁, 男性为40-49岁。SLE患病率及发病率均在西北地区最高，而华南、华东地区较低。此外，我国城镇地区SLE患者人均年医疗费用为1599.34美元，其中青少年和青年患者的医疗费用最高。

结论：在全球范围内, 中国SLE发病率较高, 且患病率增长迅速，起病年龄趋向年轻化，未来SLE将对我国的社会和经济发展造成严重负担。

第二部分  中国城镇地区类风湿关节炎的流行病学调查

背景：类风湿关节炎（rheumatoid arthritis, RA）是最常见的系统性风湿免疫病之一，具有高致残性的临床特点。中国目前缺乏基于大规模人群研究的全国患病率、发病率及相关经济负担的流行病学数据。

方法：本研究基于2013至2017年中国23个省份的城镇职工基本医疗保险和城镇居民基本医疗保险数据。采用两阶段泊松回归模型，按性别、年龄和地区分层估计RA的患病率和发病率，并对数据进行年龄和性别标准化。同时，本研究估算RA患者的年人均医疗费用和医院就诊次数等卫生经济负担指标。

结果：研究共纳入789,583名RA患者，平均年龄为54.74 (14.72)岁，其中61.25%为女性。2017年中国城镇居民RA的标准化患病率为334.35 (95%CI 288.20 - 383.92) /10万人，其中女性患病率为443.97/10万人，是男性患病率1.83倍（242.25/10万人）。5年期间RA的患病率年均增幅为21.79%。2017年的全国RA发病率为128.71(95% CI 101.69-158.91) /10万人年。患病率及发病率均在65-74岁年龄段达到峰值。南方地区的患病率、发病率低于其他地区。RA患者的人均年医疗费用估计为907.78美元。

结论：中国RA患病率存在上升趋势、较高的发病率及增长的医疗费用给社会和家庭带来了巨大的负担。

第三部分  空气污染暴露与北京市系统性红斑狼疮患者病情活动度的关联

背景：系统性红斑狼疮（SLE）是一种慢性风湿免疫性疾病，病程中出现反复的病情加重与缓解，病情活动与长期预后密切相关。空气污染作为潜在的环境风险因素，对SLE病情活动的影响目前尚未明确。

方法：本研究基于2014至2024年中国系统性红斑狼疮研究协作组登记的北京市SLE患者随访数据，评估PM_2.5、PM₁₀、NO₂、SO₂、CO、O₃共6种国家标准空气污染物与SLE疾病活动的关联。通过构建广义线性混合模型，调整年龄、性别、治疗、温度和湿度等因素，分析空气污染物对SLEDAI-2K、补体C3、抗dsDNA抗体以及尿蛋白的0-30天滞后效应。通过双污染物模型验证效应稳健性。

结果：研究对922例SLE患者的8730次随诊进行了分析。单污染物模型提示PM_2.5、PM₁₀和NO₂的短期暴露与SLEDAI-2K值呈正相关。对于每IQR浓度增加，PM_2.5的最大效应出现在滞后4天（IRR = 1.045，95% CI：1.014 - 1.077），PM₁₀的最大效应出现在滞后16天（IRR = 1.025，95% CI：1.009 - 1.041）。NO₂浓度每增加一个四分位间距（IQR，26.69 μg/m³），在5天滞后期时效应最大，发病率比（IRR）为1.074（95% CI：1.030 - 1.119）。在调整第二种污染物后，PM₁₀和NO₂仍与SLEDAI-2K值存在稳定的正相关性。SO₂的短期暴露与补体C3减低以及抗dsDNA抗体阳性相关。

结论：PM_2.5、PM₁₀和NO₂的短期暴露与SLE患者病情活动相关，而O₃和CO与SLE患者病情活动的相关性较小。本研究强调了改善空气质量对SLE患者健康管理的重要性。

第四部分  短期空气污染与中国类风湿关节炎患者病情活动的关联

背景：类风湿关节炎（RA）是一种慢性风湿免疫性疾病，其病情活动度受多种因素影响。空气污染作为潜在的环境危险因素对RA病情活动影响仍不明确。

方法：本研究基于中国类风湿关节炎直报项目登记的2014至2024年间全中国的RA患者随访数据，评估PM_2.5、PM₁₀、NO₂、SO₂、CO、O₃共6种空气污染物与RA疾病活动的关联。病情活动指标包括28关节疾病活动评分（DAS28）、临床疾病活动指数（CDAI）、简化疾病活动指数（SDAI）。对于炎症指标（CRP和ESR）及临床症状与空气污染的相关性也进行分析。本研究构建了广义线性混合模型，调整年龄、性别、治疗、合并症等因素，评估了0-30天滞后效应。通过双污染物模型评估了污染物之间的混杂效应。

结果：本研究纳入了16314例RA患者的83048次随诊。单污染物模型中PM_2.5、PM₁₀、NO₂、SO₂、CO等污染物的短期暴露均与RA活动度指标（DAS28-CRP、DAS28-ESR、CDAI、SDAI）的升高以及炎症指标、关节肿痛数显著相关。对于DAS28-CRP，CO每IQR（440μg/m³）增加，在滞后6天时效应值最大（β=0.084, 95% CI：0.072 - 0.095）；SO₂每IQR（9μg/m³）增加，最大效应出现在27天滞后时（β= 0.074，95% CI：0.063 - 0.086）。O₃在短期滞后时与RA患者病情活动负相关。双污染物模型中SO₂、CO及O₃对RA活动度的影响稳健且独立。

结论：SO₂和CO的短期暴露与RA活动具有显著而独立的正相关性。O₃在短期滞后时与RA患者病情活动负相关。本研究提示了空气污染防控对降低类风湿关节炎活动性具有重要意义。

Part 1: Epidemiological Investigation of Systemic Lupus Erythematosus in Urban China

Background: Systemic lupus erythematosus (SLE), as a chronic autoimmune disease with recurrent flares, has become a global public health concern. However, knowledge on epidemiology of SLE in developing countries is still limited.

Methods: A nationwide population-based study was conducted based on the Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance across 23 provinces in China from 2013 to 2017. SLE cases were identified using International Classification of Diseases codes and diagnostic terms. The prevalence and incidence rates of SLE, both crude and standardized, were calculated using a two-stage Poisson regression model and stratified by age, sex, and geographic region. The study also calculated the healthcare costs associated with SLE in 2017.

Results: A total of 132,258 SLE patients were included, with a mean age of 43.03 (15.29) years, of whom 81.33% were female. In 2017, the standardized prevalence rates of SLE in the total population, females, and males were 47.61, 94.16, and 17.86 per 100,000 people, respectively. Over the five-year study period, the annual increase in SLE prevalence was 21.50%. The standardized incidence rate of SLE in urban China in 2017 was 14.09 per 100,000 person-years (95% CI: 11.95-16.41), with a higher rate in females (26.41 per 100,000 person-years) than in males (5.92 per 100,000 person-years). SLE prevalence and incidence rates in 2017 displayed a unimodal distribution by age, reaching their peak in females aged 30-39 and males aged 40-49. The highest prevalence and incidence rates were observed in Northwest China, and the lowest in Southern and Eastern China. The average annual per-capita healthcare cost was $1,599.34, with the highest costs observed among adolescent and young adult patients.
    Conclusion: China has a high incidence of SLE, with a rapidly increasing prevalence, younger age of onset. SLE imposes heavy socioeconomic burden on China’s healthcare system.
    

Part 2: Epidemiological Investigation of Rheumatoid Arthritis in Urban China

Background: Rheumatoid arthritis (RA) is one of the most common systemic autoimmune rheumatic diseases, characterized by high disability rates and is a major cause of disability in the Chinese population. However, there is a lack of nationwide data on prevalence, incidence, and associated economic burden of RA from large-scale population-based studies in China.

Methods: This study utilized data from the Urban Employee Basic Medical Insurance and Urban Resident Basic Medical Insurance across 23 provinces in China from 2013 to 2017. A two-stage Poisson regression model was employed to estimate the prevalence and incidence rates of RA, stratified by sex, age, and region. The rates were age- and sex-standardized. The study estimated the annual per-capita medical costs and hospital visit frequencies to assess the economic burden of RA.

Results: A total of 789,583 RA patients were identified, with a mean age of 54.74±14.72 years, of whom 61.25% were female. In 2017, the standardized prevalence rate of RA in urban China was 334.35 per 100,000 people (95% CI: 288.20-383.92), with the prevalence in females (443.97 per 100,000) nearly twice that in males (242.25 per 100,000). The annual increase during the study period in RA prevalence was 21.79%. The national incidence rate of RA in 2017 was 128.71 per 100,000 person-years (95% CI: 101.69-158.91). Both prevalence and incidence rates by age peaked in the 65-74 age group. The prevalence and incidence rates were lower in Southern China compared to other regions. The annual per-capita medical cost for RA patients was $907.78.

Conclusion: The rising prevalence, high incidence, and increasing medical costs of RA impose a significant burden on society.

Part 3: Association Between Air Pollution Exposure and Disease Activity in Systemic Lupus Erythematosus patients in Beijing

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterized by recurrent exacerbations and remissions, which can significantly impact long-term prognosis. The impact of air pollution on disease activity, as an important environmental factor, remains unclear.

Methods: This study utilized data from SLE patients in Beijing registered in the Chinese Systemic Lupus Erythematosus Research Collaboration (CSTAR) from 2014 to 2024. We evaluated the associations between six air pollutants (PM_2.5, PM₁₀, NO₂, SO₂, CO, and O₃) and SLE disease activity. A generalized linear mixed model was constructed to analyze the 0–30 day lag effects of air pollutants on SLEDAI-2K, complement C3, anti-dsDNA antibodies, and proteinuria, adjusting for confounding factors including age, sex, treatment, temperature, and humidity. The robustness of the effects was validated using a two-pollutant model.

Results: A total of 9,230 follow-up visits from 922 SLE patients were included. Short-term exposure to PM_2.5, PM₁₀, and NO₂ were positively associated with the SLEDAI-2K score in the single pollutant model. For each IQR increase in concentration, the maximum effect of PM_2.5 occurred at a 4-day lag (IRR = 1.045, 95% CI: 1.014 - 1.077), while the maximum effect of PM₁₀ was observed at a 16-day lag (IRR = 1.025, 95% CI: 1.009 - 1.041). For an interquartile range (IQR) increase of 26.69 μg/m³ in NO₂, the highest incidence rate ratio (IRR) for SLEDAI-2K (lag 5 days) was 1.074 (95% CI: 1.030 - 1.119). When adjusted for a second pollutant, the positive associations between PM₁₀, NO₂, and SLEDAI-2K remained robust. Short-term exposure to SO₂ was associated with decreased complement C3 levels and positive anti-dsDNA antibody.

Conclusion: Short-term exposure to PM_2.5, PM₁₀, and NO₂ was associated with increased disease activity in SLE patients. This study highlights the importance of improving air quality in the health management of SLE patients.

Part 4: Association Between Short-term Air Pollution Exposure and Disease Activity in Patients with Rheumatoid Arthritis in China

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease with various factors inflecting its disease activity. Air pollution has been suggested as a potential environmental risk factor, but its impact on RA disease activity remains unclear.

Methods: This study utilize nationwide follow-up data from RA patients registered in the Chinese Registry of Rheumatoid Arthritis (CREDIT) from January 2014 to October 2024 to evaluate the association between six major air pollutants (PM₂.₅, PM₁₀, NO₂, SO₂, CO, and O₃) and RA disease activity. Disease activity indicators included the 28-joint disease activity score (DAS28), clinical disease activity index (CDAI), and simplified disease activity index (SDAI). Associations between air pollution and inflammatory markers as well as clinical symptoms were analyzed. A generalized linear mixed model was constructed to assess the lag effects (0–30 days) of air pollutants on RA disease activity while adjusting for potential confounders, including age, sex, treatment, and comorbidities. A two-pollutant model was further applied to evaluate potential interactions and confounding effects between pollutants.

Results: A total of 16,314 RA patients with 83,048 follow-up visits from 323 cities were included in the analysis. The single-pollutant model showed that short-term exposure to PM_2.5, PM₁₀, NO₂, SO₂, and CO was significantly associated with increased RA disease activity indices (DAS28-CRP, DAS28-ESR, CDAI, and SDAI) as well as elevated inflammatory markers and swollen/tender joint counts. CO exhibited the strongest effect on DAS28-CRP in a 6-day lag, with an interquartile range (IQR, 440μg/m³) increase associated with a β coefficients of 0.084 (95% CI: 0.072 - 0.095). For each IQR increase in concentration (9μg/m³), the maximum effect of SO₂ on DAS28-CRP occurred at a 27-day lag (β= 0.074, 95% CI: 0.063 - 0.086). Short-term exposure to O₃ was negatively associated with disease activity in RA patients. In the two-pollutant model, the associations of SO₂, CO and O₃ with RA disease activity remained robust.

Conclusion: Short-term exposure to SO₂ and CO was robustly and independently associated with increased RA disease activity, while O₃ was negatively associated with disease activity. These findings underscore the importance of air pollution control measures.